Linked Life Data

9516378

Source:http://linkedlifedata.com/resource/pubmed/id/9516378

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-6-4
pubmed:abstractText
Macrophage Inflammatory Protein (MIP)-1alpha is myelosuppressive in vitro and in vivo for hematopoietic stem and immature subsets of myeloid progenitor cells, demonstrates some myeloprotective effects in mice treated with Ara-C and hydroxyurea, and has stem/progenitor cell mobilizing activity in mice. Based on these observations, BB10010, a genetic variant of MIP-1alpha, was assessed for effects on marrow and blood myeloid progenitor cells in patients with relapsed/refractory breast cancer. MIP-1alpha readily polymerizes, whereas BB10010 has a reduced tendency to form large polymers at physiological pH and ionic strength and retains biological activity. Patients were injected with 5, 10, 30 or 100 microg/kg BB10010 s.c. daily for 3 days. BB10010 significantly reduced the cycling status of marrow myeloid progenitors from pretreatment levels of 39-58% to 0 - 11% one day after the third and last injection of BB10010. This was associated with significant decreases in frequency of marrow progenitors (number of colonies formed per number of cells plated) and percent biopsied marrow CD34+ cells. The suppressive effects were reversible in patients and the rapidity of this reversal demonstrated in mouse studies. BB10010 had no effect on nucleated cellularity or on the proliferation of nucleated cells as assessed in marrow biopsies from the patients. These latter effects may in part reflect the noted decreased apoptosis of nucleated cells by BB10010. BB10010 also demonstrated significant but modest myeloid progenitor cell mobilizing capacity. Blood progenitors were in a slow or non-cycling state prior to treatment and this did not change after administration of BB10010. The above effects of BB10010 were similar at the four different dosage levels assessed. These results demonstrate in humans the suppressive and mobilizing effects of MIP-1alpha and BB10010 previously noted in vivo in mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1079-9796
pubmed:author
pubmed:copyrightInfo
Copyright 1998 The Blood Cells Foundation.
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14-30
pubmed:dateRevised
2010-5-10
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Myeloid progenitor cell proliferation and mobilization effects of BB10010, a genetically engineered variant of human macrophage inflammatory protein-1alpha, in a phase I clinical trial in patients with relapsed/refractory breast cancer.
pubmed:affiliation
Department of Microbiology/Immunology and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA. hal_broxmeyer@iucc.iupui.edu
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Clinical Trial, Phase I